The synthesis of a wide variety of water-soluble porphyrins containing the o-carborane group, 1,2-B10C2H12, is proposed using six different synthetic organic methodolgies. These include (I) Rothemund condensations of carboranyl aldehydes, (II) carboranyl-amido-linked porphyrins from meso-tetra (aminophenyl)porphyrins, (III) Rothemund condensations of carboranylbenzaldehydes, (IV) billadienes-ac condensations with carboranyl aldehydes, (V) nucleophilic and elctrophilic reactions of carborane derivatives on natural porphyrins or their derivatives, and (IV) the total synthesis Beta-carboranyl porphyrins. In classes (I)-(IV) water solubility is to be achieved by the subsequent addition of four different water-solubilizing groups, while in (IV) and (V) it is achieved by the Beta-pyrole propionic acid groups of natural porphyrins. Biomedical evaluation of these compounds will include toxicological and tumor-localization studies carried out by a group at Brookhaven National Laboratories. In suitable cases this will be followed by neutron capture therapy experimental trials in animals. No funds are requested for such testing since the BNL group is already fully supported by the Department of Energy to perform this testing. Protocols for these studies are described. The over-all objectives of the proposed work is to prepare boronated porphyrins which will selectively accumulate in tumor cells. The use of boron compounds in the treatment of cancer is based on the unique ability of non-radioactive 10B to absorb thermal (low energy) neutrons. The prompt nuclear reactions which occur on thermal neutron absorption deliver a dose of nearly 2.8 NEV only in the vicinity of boron-containing cells since the nuclear fragments produced (alpha particles and lithium atoms) travel only 10-15 um. Porphyrins of both natural and synthetic origin have been shown by a number of investigators to accumulate in neoplastic tissue. Such localization forms the basis for current clinical phototherapy of a variety of concerns. Preliminary work by the author has resulted in the synthesis of several novel carborane porphyrins. One of these is found to localize in the malanoma mouse model system and used for preliminary screening at BNL in therapeutically significant amounts and over a time course significantly better than Na2B12H11SH, the borane in current clinical use in Japan. In light of these encouraging results, funds are requested to support a significant broadening of the synthetic chemical effort at UCSF.